E-viri
PDF
Recenzirano
Odprti dostop
-
Liu, Lili; Mladkova, Nikol; Li, Yifu; Ren, Hong; Wang, Weiming; Cui, Zhao; Lin, Li; Yu, Xialian; Xu, Jing; Liu, Gang; Balderes, Olivia; Rosen, Raphael J; Bodria, Monica; Zanoni, Francesca; Zhang, Jun Y; Krithivasan, Priya; Mehl, Karla; Marasa, Maddalena; Ozay, Fatih; Canetta, Pietro A; Bomback, Andrew S; Appel, Gerald B; Sanna-Cherchi, Simone; Sampson, Matthew G; Mariani, Laura H; Perkowska-Ptasinska, Agnieszka; Durlik, Magdalena; Mucha, Krzysztof; Moszczuk, Barbara; Foroncewicz, Bartosz; Pączek, Leszek; Habura, Ireneusz; Ars, Elisabet; Ballarin, Jose; Mani, Laila-Yasmin; Vogt, Bruno; Ozturk, Savas; Yildiz, Abdülmecit; Seyahi, Nurhan; Arikan, Hakki; Koc, Mehmet; Basturk, Taner; Akgul, Sebahat Usta; Sever, Mehmet Sukru; Santoro, Domenico; Bonomini, Mario; Gesualdo, Loreto; Reiterova, Jana; Tesar, Vladimir; Izzi, Claudia; Savoldi, Silvana; Spotti, Donatella; Marcantoni, Carmelita; Messa, Piergiorgio; Galliani, Marco; Roccatello, Dario; Granata, Simona; Zaza, Gianluigi; Lugani, Francesca; Ghiggeri, GianMarco; Pisani, Isabella; Allegri, Landino; Sprangers, Ben; Park, Jin-Ho; Kim, Yon Su; Kim, Dong Ki; Suzuki, Hitoshi; Amoroso, Antonio; Cattran, Daniel C; Fervenza, Fernando C; Hamilton, Patrick; Harris, Shelly; Gupta, Sanjana; Powis, Stephen; Bockenhauer, Detlef; Stanescu, Horia C; Ashman, Neil; Loos, Ruth J F; Kenny, Eimear E; Wuttke, Matthias; Eckardt, Kai-Uwe; Köttgen, Anna; Hofstra, Julia M; Coenen, Marieke J H; Kiemeney, Lambertus A; Akilesh, Shreeram; Beck, Lawrence H; Debiec, Hanna; Ronco, Pierre; Wetzels, Jack F M; Zoledziewska, Magdalena; Cucca, Francesco; Ionita-Laza, Iuliana; Hoxha, Elion; Stahl, Rolf A K; Scolari, Francesco; Gharavi, Ali G; Kleta, Robert; Chen, Nan; Kiryluk, Krzysztof
Nature communications, 03/2020, Letnik: 11, Številka: 1Journal Article
Membranous Nephropathy (MN) is a rare autoimmune cause of kidney failure. Here we report a genome-wide association study (GWAS) for primary MN in 3,782 cases and 9,038 controls of East Asian and European ancestries. We discover two previously unreported loci, NFKB1 (rs230540, OR = 1.25, P = 3.4 × 10 ) and IRF4 (rs9405192, OR = 1.29, P = 1.4 × 10 ), fine-map the PLA2R1 locus (rs17831251, OR = 2.25, P = 4.7 × 10 ) and report ancestry-specific effects of three classical HLA alleles: DRB1*1501 in East Asians (OR = 3.81, P = 2.0 × 10 ), DQA1*0501 in Europeans (OR = 2.88, P = 5.7 × 10 ), and DRB1*0301 in both ethnicities (OR = 3.50, P = 9.2 × 10 and OR = 3.39, P = 5.2 × 10 , respectively). GWAS loci explain 32% of disease risk in East Asians and 25% in Europeans, and correctly re-classify 20-37% of the cases in validation cohorts that are antibody-negative by the serum anti-PLA2R ELISA diagnostic test. Our findings highlight an unusual genetic architecture of MN, with four loci and their interactions accounting for nearly one-third of the disease risk.
